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Activity Number: 343 - SPEED: Tests, Trials, Biomarkers, and Other Topics in Biometrics
Type: Contributed
Date/Time: Tuesday, July 31, 2018 : 10:30 AM to 12:20 PM
Sponsor: Biopharmaceutical Section
Abstract #330415
Title: Functional Data Analysis in Dose-Adjusted Tacrolimus Trough Concentration Modeling: A New Method to Compare Intrapatient Variance Between Patient Cohorts
Author(s): Janet Kim* and Sam Wilson and Jason J Schwartz
Companies: Astellas Pharma Global Development, Inc. and Astellas Pharma Global Development, Inc. and Astellas Pharma Global Development, Inc.
Keywords: Intrapatient variability; Functional data; Functional principal component analysis; Two-sample test

Active research in immunosuppressive therapies assesses within-patient therapeutic blood concentrations fluctuating over time. Consequently, intrapatient variability (IPV) estimates relying on fixed dose assumption/linear statistical models may be inaccurate. To address this issue, a recently developed, dose-adjusted tacrolimus trough concentration (TTC) model utilizes a flexible class of functional regression models, treating longitudinal TTC and dose information as a realization of a stochastic process observed at discrete times. Dose-adjusted TTC variance is derived using standard functional principal component analysis (FPCA). This study proposes formal testing to compare subgroup IPVs based on the above framework. We decompose residual process from the model using FPCA, and estimate the covariance of error process by finite rank approximation. This reduces the infinite dimensional two-sample functional testing problem to a finite dimensional problem, allowing any nonparametric univariate tests. Numerical studies show excellent test properties under various settings. A comprehensive summary will be reported based on data from Phase III studies with prolonged-release tacrolimus.

Authors who are presenting talks have a * after their name.

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